Fig. 4.

Final model structure of semi-mechanistic multiple-analyte population model for MMAE containing ADCs. ADC: antibody-drug conjugate; CLd: distributional clearance of ADC; CLm: systemic clearance of unconjugated MMAE from the central compartment; CLmd: distributional clearance of unconjugated MMAE; DAR8c, DAR7c, … DAR1c, DAR0c: concentrations of anti-CD79b-MMAE ADC in the central compartment with DAR = 0–8; DAR8p, DAR7p, … DAR1p, DAR0p: concentrations of anti-CD79b ADC in the peripheral compartment with DAR = 0–8; Emax: maximal target-mediated proteolytic degradation rate of ADC; Fmd: fraction of formation of unconjugated MMAE in the central compartment from the deconjugation pathway of ADC; Fmp: fraction of formation to unconjugated MMAE in the central compartment from the proteolytic degradation pathway of ADC; KADC8, KADC7, …KADC1: deconjugation rate constants for each DAR species (DAR = 8, 7, …, 1) of the ADC; Km: concentration of ADC to reach half of the maximal Emax; MMAEc: concentration of unconjugated MMAE in the central compartment; MMAEp: concentration of unconjugated MMAE in the peripheral compartment; Vc: central volume of distribution for ADC; Vp: peripheral volume of distribution for ADC; Vm: central volume of distribution for unconjugated MMAE; Vmp: peripheral volume of distribution for unconjugated MMAE